Papillary Tumors of the Pineal Region

CASE REPORTS PAPILLARY TUMORS OF THE PINEAL REGION: CASE REPORT Elias Dagnew, M.D. Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Lauren A. Langford, M.D. Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Frederick F. Lang, M.D. Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Franco DeMonte, M.D. Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas Reprint requests: Elias Dagnew, M.D., 9802 Baymeadows Road, #12–148, Jacksonville, FL 32256. Email: [email protected] OBJECTIVE: The pineal region is a rare intracranial site for metastasis. We report three patients initially considered to have metastatic papillary adenocarcinoma to the pineal region. On review, these papillary, keratin-positive neoplasms meet the criteria for papillary tumor of the pineal region (PTPR). CLINICAL PRESENTATION: These neoplasms occurred in three women (age range, 37–55 yr). Imaging studies demonstrated well-circumscribed lesions in the pineal region. All patients presented with obstructive hydrocephalus and symptoms attributable to hydrocephalus and tectal compression. INTERVENTION: All three patients underwent near total microsurgical resection of the pineal region neoplasm, followed by adjuvant radiotherapy. The two patients with longterm follow-up (56–60 mo) have remained clinically stable without evidence of local or distant recurrence. The first two patients were initially diagnosed as having papillary metastatic carcinoma of unknown origin. The third patient was treated after the recent description of PTPR and met the histopathological diagnostic criteria. Retrospective pathological review of the previous two patients resulted in designation as PTPR. CONCLUSION: The morphological features of the tumors in our series, along with the clinical presentations, are similar to those in the original description of the PTPR. Our findings agree with the original hypothesis that the cells composing the PTPR are similar to ependymal cells of the subcommissural organ, thus furthering the hypothesis that the PTPR derives from a specialized ependymocyte associated with the subcommissural organ. The two patients with long-term follow-up (56–60 mo) have remained clinically stable without evidence of local or distant recurrence. KEY WORDS: Ependymoma, Metastasis, Papillary tumor, Pineal region, Subcommissural organ Neurosurgery 60:E953–E955, 2007 DOI: 10.1227/01.NEU.0000255443.44365.77 www.neurosurgery-online.com Received, June 4, 2006. Accepted, January 12, 2007. T umors of the pineal region are relatively rare neoplasms that comprise 1% or less of all intracranial neoplasms (13, 14). Tumors in this region have diverse origins, including tumors arising from pineal parenchymal cells (i.e., pineocytoma and pineoblastoma), pineal cysts, tumors of germ cell origin (i.e., teratoma, germinoma, yolk sac tumor, and choriocarcinoma), ependymoma, meningioma, astrocytoma, and, rarely, metastases. Tumors of the central nervous system demonstrating papillary features are rare (7). It is known that the presence of papillary features in central nervous system lesions presents a wide spectrum of pathological differential diagnostic possibilities, including papillary ependymoma, choroid plexus tumor, primary germ cell tumor, meningioma, medulloepithe- NEUROSURGERY lioma, astroblastoma, and metastatic papillary carcinoma (1, 14). The most frequently encountered papillary tumors are papillary ependymoma, choroid plexus tumors, and metastatic papillary carcinoma (1). Primary papillary tumors of the pineal region (PTPR) are extremely rare. Our review of the literature identified two case reports of papillary pineocytoma (13, 14), a case report of a papillary ependymoma (10), and a recent report of six patients with pineal region papillary tumors demonstrating consistent histopathological characteristics that seem to define a distinct subtype of papillary tumors, appropriately designated by the authors as PTPR (7). We report our experience with three patients with pineal region tumors with papillary features who were diagnosed and treated at our VOLUME 60 | NUMBER 5 | MAY 2007 | E953 DAGNEW ET AL. A B FIGURE 1. Patient 1. Preoperative sagittal (A) and axial (B) T1-weighted gadolinium-enhanced MRI scans demonstrating a 2.5-cm heterogeneously enhancing mass in the pineal region. The patient had undergone VPS placement before this MRI scan. institution. The first two patients were initially diagnosed as having papillary metastatic carcinoma of unknown origin. After the recent description of the features of PTPR, the third patient was treated at our institution and was noted to meet the histopathological diagnostic criteria for PTPR. Retrospective pathological review of the previous two patients resulted in designation of these cases as PTPR on the basis of specific histopathological criteria. Here, we describe in detail the presentation, clinical course, management, and follow-up, and describe the histopathological characteristics of the three cases of pineal region tumors with papillary features, which we think meet the histopathological criteria for the recently described entity, PTPR. ILLUSTRATIVE CASES Patient 1 A 37-year-old woman presented to an outside medical institution with a 1-year history of left-sided headache and intermittent visual loss. General physical and neurological examination demonstrated normal findings except for bilateral papilledema. Magnetic resonance imaging (MRI) scans of the brain demonstrated a 2.5-cm, heterogeneously enhancing, well-demarcated mass in the pineal region with mild surrounding vasogenic edema and associated obstructive hydrocephalus (Fig. 1). The patient underwent the placement of a ventriculoperitoneal shunt (VPS), with complete resolution of her symptoms and the hydrocephalus. Open biopsy was undertaken, with a frozen section diagnosis of a germinoma. Further review of the pathological specimen on permanent section led to diagnosis of a choroid plexus papilloma (CPP). Re-review of the pathological specimen at our institution led to a pathological diagnosis of metastatic adenocarcinoma. A complete metastatic work-up was undertaken, and the results were negative. The patient underwent a supracerebellar infratentorial approach with near total surgical resection of the pineal region mass. This was followed by adjunctive stereotactic radiosurgery (SRS) to 15 Gy at the 85% isodose line, administered 1 month after surgical resection. Frozen and permanent sections were interpreted as papillary adenocarcinoma. Immunohistochemical stains indicated a strongly positive immunoreactivity to cytokeratin, neuron-specific enolase (NSE), and vimentin, with weak immunoreactivity for epithelial membrane antigen (EMA). Immunoreactivity was negative for synaptophysin, glial fibrillary acidic protein (GFAP), and transthyretin. Variable E953 | VOLUME 60 | NUMBER 5 | MAY 2007 FIGURE 2. Light microscopy of smear preparation. Hematoxylin and eosin staining in PTPR demonstrating many cells of the signet-ring type (arrow). The intracytoplasmic mucin droplet is noted to indent the nucleus. Original magnification, ⫻40. immunoreactivity for S-100 protein was noted. Furthermore, many cells of signet-ring type were visible (Fig. 2). The patient remains neurologically stable with mild upward gaze paresis on the left and maintains a stable small residual disease on brain MRI scans 60 months after surgery. Patient 2 A 51-year-old woman presented with a 3-year history of fatigue, confusion, short-term memory loss, right-sided weakness, and unsteadiness of gait. Two weeks before her presentation, she had a rapid deterioration of her gait. Preoperative examination revealed decreased upward gaze, nystagmus, and a broad-based gait. A T1-weighted MRI scan revealed a well-defined, 2.3-cm macrolobulated pineal region tumor, with significant compression of the tectum and cerebral aqueduct and resultant hydrocephalus (Fig. 3). An external ventricular drain was placed, and the patient underwent a supracerebellar infratentorial approach with near total resection of the pineal region mass. Histopathology revealed a malignant neoplasm with a diagnosis of metastatic adenocarcinoma. The neoplastic cells were noted to be immunoreactive for cytokeratin, NSE, vimentin, and S-100, A B FIGURE 3. Patient 2. Preoperative sagittal (A) and axial (B) T1-weighted gadolinium-enhanced MRI scans demonstrating a 2.3-cm macrolobulated pineal region tumor with significant compression of the tectum and aqueduct, resulting in hydrocephalus. www.neurosurgery-online.com PAPILLARY PINEAL REGION TUMORS A B FIGURE 4. Patient 3. Preoperative coronal (A) and sagittal (B) T1-weighted MRI scans after gadolinium administration demonstrating a 2-cm heterogeneously enhancing, partially cystic mass in the posterior third ventricular/ pineal region. The patient had initially presented with obstructive hydrocephalus and underwent placement of a VPS before this MRI scan. and negative for synaptophysin, GFAP, and transthyretin. Weak immunoreactivity to EMA was noted. Some mitotic figures were notable in the histological specimen, and MIB-1 immunostaining showed scattered labeled tumor cell nuclei. The patient underwent adjunctive whole-brain radiotherapy (30 Gy in 10 fractions) 2 weeks after surgical resection. Results from a thorough metastatic work-up were negative. On the last follow-up examination at 56 months after surgery, the patient was neurologically intact and an MRI scan of the brain demonstrated a stable small residual. Patient 3 A 54-year-old woman presented to an outside institution with a 3-week history of severe headache and short-term memory loss. An MRI scan of the brain revealed a 2-cm heterogeneously enhancing, partially cystic mass in the posterior third ventricle and pineal region (Fig. 4). There was evidence of obstructive hydrocephalus. The patient underwent placement of a VPS, with resolution of symptoms. The patient subsequently underwent a frameless image-guided transcallosal-transventricular near total resection of the pineal region mass. The patient’s postoperative course was complicated by a small left frontal venous infarct and speech hesitancy, which had completely resolved at time of the last follow-up examination. Histopathological evaluation of the neoplasm demonstrated a mixture of papillary pattern in some regions and signet-ring cell-containing solid areas in other regions. Immunostaining was positive for cytokeratin, NSE, vimentin, and S-100 protein, and negative for synaptophysin and GFAP. Variable and weak staining for EMA and transthyretin was noted. These characteristics fit the diagnostic criteria for the recently described PTPR. The patient underwent SRS to the residual tumor (15 Gy delivered at the 85% isodose line) 3 weeks after surgery. The patient’s follow-up study is being conducted in her native country in Europe. DISCUSSION Lesions in the pineal region commonly present a diagnostic dilemma because of the occurrence of differing histopathological entities in this region. The correct histopathological diagnosis of a neoplasm arising in the pineal region often cannot be determined on the basis of imaging characteristics or cerebrospinal fluid sampling (13). Definitive diagnosis is usually made after direct microscopic examination of tissue obtained NEUROSURGERY by surgical intervention (e.g., biopsy or resection). The recognition of papillary features in a pineal region neoplasm narrows the differential diagnosis to metastatic carcinoma, papillary ependymoma, choroid plexus tumors, germ cell tumors, papillary meningioma, and a rare subtype of pineal parenchymal tumor, papillary pineocytoma (13, 14). In the first two patients in our report, the initial histopathological diagnosis was that of metastatic adenocarcinoma of unknown primary because, despite extensive metastatic work-up, a primary site of the tumor origin was not identified. Immunohistochemical analysis in both of these patients demonstrated strong immunoreactivity for cytokeratin, NSE, and vimentin, and weak (EMA) or no immunoreactivity (synaptophysin and GFAP) to other markers, excluding such entities as pineal parenchymal tumor, ependymoma, or tumors of glial origin. In Patient 2, an outside institution biopsy had suggested a CPP. However, the lack of strong immunoreactivity for transthyretin and EMA, and the presence of significant pleomorphism and signet cells were not consistent with this diagnosis. CPPs generally do not have signet cells and they demonstrate strong immunoreactivity for transthyretin and EMA. Furthermore, the presence of signet cells weighs heavily toward the diagnosis of carcinoma, regardless of the immunostain, although the diagnosis of metastatic adenocarcinoma to the pineal region is a very rare entity, constituting only 3 to 4% of both intracranial metastases (4, 6) and pineal region tumors (2, 8, 11), with adenocarcinoma pathology constituting a smaller percentage of all metastasis that can occur in the region (65–79%) (9, 12). Histopathology The recent description of six patients with a unique subtype of pineal region tumors with papillary features by Jouvet et al. (7) has shed light on a new diagnostic entity. The microscopic and immunohistochemical features of these tumors are unique and differentiate them from the histopathologically confusing group of central nervous system tumors with papillary features. Microscopically, these neoplasms demonstrated diffuse cellular proliferation with large areas demonstrating papillary features and well-formed glands. The cellular structures demonstrate cells that have a moderate amount of eosinophilic cytoplasm and mildly nonuniform round-to-oval nuclei with a prominent basophilic nucleolus (Fig. 5). Signet ring cells may be present. Pseudorosette formation may be present, although not sufficiently well formed or prevalent to support a diagnosis of ependymoma. Moderate mitotic figures were notable. Immunohistochemical studies demonstrated dramatic immunoreaction in the PTPR neoplastic cells against cytokeratin, S-100 protein, NSE, and vimentin, whereas the PTPR neoplastic cells were not immunoreactive for synaptophysin and had variable staining for EMA (Fig. 6, A–D). The GFAP immunohistochemical staining showed occasional immunoreactive cells but these cells had characteristics of entrapped reactive astrocytes. No GFAP-immunoreactive tumor cells were detected in any of these patients (Fig. 6E). Transthyretin showed a few weakly immunoreactive cells. VOLUME 60 | NUMBER 5 | MAY 2007 | E954 DAGNEW ET AL. A B C FIGURE 5. Light microscopy (hematoxylin and eosin staining) demonstrating features of PTPR. A, abundant hypercellular areas with papillary features. B, cells with mildly nonuniform round-tooval nuclei. Furthermore, well-formed rosettes are notable. C, higher magnification demonstrating cells with round or oval nuclei and prominent basophilic nucleoli, with rosette formation. Original magnification, ⫻4 (A), ⫻10 (B), and ⫻40 (C). A B C D E FIGURE 6. Immunohistochemical staining in PTPR. A, intense immunoreactivity for cytokeratin was seen in all cases. B, higher magnification demonstrating immunoreactivity to cytokeratin. Striking immunoreactivity to S-100 protein (C) and weaker immunoreactivity to EMA (D) was seen in all cases. E, PTPR cells did not express GFAP, although reactive astrocytes processes are GFAP immunoreactive (arrow). Original magnification, ⫻4 (A and D) and ⫻10 (B, C, and E). Our patients demonstrated findings congruent with those of Jouvet et al. (Table 1) (7). Patient 3 in our series underwent surgical resection after the report by Jouvet et al. (7) and was noted to meet the diagnostic criteria for PTPR. Retrospective review and further immunohistochemical studies on tissue from Patients 1 and 2 demonstrated findings consistent with this recently described entity. Although some of the morphological features in PTPR can be found in other neoplasms with papillary features, there are unique identifying features that help in correctly diagnosing this entity. Among the more com- E954 | VOLUME 60 | NUMBER 5 | MAY 2007 mon differential diagnoses to consider is papillary ependymoma. However, although ependymomas express positive immunoreactivity for GFAP and not cytokeratin, PTPRs are GFAP negative and cytokeratin positive (1, 7). Another differential to consider is choroid plexus tumors (CPP and choroid plexus carcinoma). Although choroid plexus tumors, similar to PTPRs, are immunoreactive for cytokeratin, the immunoreactivity to the other markers is not consistent with PTPR. Choroid plexus tumors demonstrate strong immunoreactivity to EMA, whereas PTPRs demonstrate no or weaker reactivity www.neurosurgery-online.com PAPILLARY PINEAL REGION TUMORS A TABLE 1. Immunohistochemical and structural characteristics of papillary pineal region tumorsa Patient 1 Patient 2 Patient 3 Jouvet et al. (7) Cytokeratin ⫹ ⫹ ⫹ ⫹ NSE ⫹ ⫹ ⫹ ⫹ Vimentin ⫹ ⫹ ⫹ ⫹ EMA ⫹b ⫹b ⫹b ⫹/–b S-100 ⫹ ⫹ ⫹ ⫹ GFAP – – – –c Transthyretin – – ⫹d n/a Synaptophysin – – – – Signet ring cells ⫹ ⫹ ⫹ ⫹ a +, positive immunoreactivity; NSE, neuron-specific enolase; EMA, epithelial membrane antigen; –, negative immunoreactivity; GFAP, glial fibrillary acidic protein; n/a, not available. b Very weak or no immunoreactivity for EMA was noted in all cases. c Some positive immunoreactivity of reactive astrocytes was noted. d Few weakly immunoreactive cells were noted. B to EMA. Furthermore, choroid plexus tumors demonstrate strong immunoreactivity to transthyretin, whereas PTPRs typically demonstrate negative or weak immunoreactivity for transthyretin. The cellular structure of PTPR shows them to be less papillary than CPP but significantly more differentiated than would be expected for choroid plexus carcinoma (7). On the other hand, these lesions can microscopically resemble metastatic adenocarcinomas. However, adenocarcinomas rarely demonstrate immunoreactivity for proteins such as vimentin, NSE, and S-100 protein, which were all immunoreactive in PTPR (1, 7). Finally, the fact that our patients demonstrated negative immunoreactivity for synaptophysin pointed against a pineal parenchymal tumor (1). In our cases, electron microscopy supports the report by Jouvet et al. (7) regarding the likely secretory nature and ependymal origin of these cells. The ultrastructure of the tumor cells demonstrated irregular nuclear contours and focal prominent nucleoli. The cytoplasm contained abundant mitochondria, bundles of intermediate filaments, and lipid droplets. Cell edges had extensive microvillous processes as well as prominent elongated intracellular junctions (Fig. 7). The presence of abundant rough endoplasmic reticulum and granular secretory material with dilated cisternae suggest a secretory function (as seen in choroid plexus cells) but the presence of microvilli and zipper-like intracellular junctions suggest ependymal differentiation (7). The origin of these neoplasms has been speculated to be from the subcommissural organ (SCO) because their location and morphological features are closely related to the specialized ependymal cells of the SCO (7). The ependymal cells found in the infant SCO are typically immunoreactive for cytokeratin, EMA, and S-100 protein, negative for GFAP and transthyretin, and demonstrate numerous secretory organelles (7). These NEUROSURGERY FIGURE 7. A and B, electron microscopic images (sagittal plane) of a representative case demonstrating the ultrastructure of PTPR. Cells demonstrated irregular nuclear contours and focal prominent nucleoli. Furthermore, the cytoplasm contained numerous mitochondria and rough endoplasmic reticulum. Bundles of intermediate filaments were present in the cytoplasm of some cells. The cell edges had extensive microvillous processes as well as prominent elongated cell-to-cell junctions. ependymal cells can remain vestigial in the adult SCO and may be involved in the histogenesis of the PTPR. Clinical Course The biological behavior, natural course, and appropriate therapy for these recently described rare entities is not clear because there are only a few described cases and limited follow-up studies. Of the three cases reported in our series, two VOLUME 60 | NUMBER 5 | MAY 2007 | E954 DAGNEW ET AL. patients (Patients 1 and 2) had follow-up periods of 56 and 60 months, respectively, after resection followed by adjuvant, SRS or whole-brain radiotherapy. At the time of the last follow-up examination, both patients had stable residual disease, without evidence of dissemination in the craniospinal axis. Patient 3 had only a short follow-up period (⬍3 mo) and, hence, data was not available for review. The first two patients in our series were initially diagnosed as having metastatic adenocarcinoma of unknown origin. The clinical outcome of these patients is not typical of patients with brain metastases of unknown origin. Although the patients remained alive and without recurrence for a follow-up period of 56 to 60 months, patients with brain metastasis of unknown origin achieve a median survival of only 13.4 months (9), with rare longer-term survivors. Jouvet et al. (7) gave a limited report of the clinical follow-up and outcome in the six patients reported in their study. During a follow-up period of 16 to 57 months, four patients had local recurrence and one patient had spinal dissemination. Meanwhile, one patient who underwent partial resection and adjuvant SRS had good local disease control at the resection site after 23 months of follow-up. Although all patients had received radiotherapy at some time in the course of their treatment, their study did not specifically outline whether or not radiotherapy was used after surgical resection or at recurrence. The limited data available suggests that PTPRs seem to behave similar to such entities as ependymoma and CPP, with a potential propensity for local recurrence and rare potential for craniospinal dissemination. Our limited initial experience with two patients managed with a locally aggressive regimen of near total resection followed by adjuvant radiotherapy has shown excellent local control at 56 and 60 months after resection. Furthermore, despite the potential for local recurrence, patients in our series and in the report by Jouvet et al. (7) remained alive during the extent of the follow-up period (3–60 mo), and, hence, seem to achieve long-term survival after appropriate surgical and adjuvant radiotherapy. Longer follow-up periods and the accrual of further case reports are needed to define the natural course and survival of patients diagnosed with PTPR. Because of the potential for local recurrence noted in the small series available and the excellent local control achieved in our two patients treated with aggressive local therapy, we advocate maximal surgical resection followed by adjuvant radiotherapy in the form of SRS or fractionated three-dimensional conformal radiotherapy. Furthermore, we advocate cerebrospinal fluid sampling and spinal survey MRI scans to exclude the possibility of craniospinal dissemination. Craniospinal radiotherapy should be withheld if there is lack of evidence of dissemination. Because of the unknown natural history of these tumors and the suggestion of an increased chance of local recurrence, we advocate close imaging follow-up with MRI scans of the brain at 3-month intervals during the first year after resection and yearly thereafter. Whether or not these tumors undergo further dedifferentiation to more malignant tumors is unknown. This series, together with the report by Jouvet et al. (7), describes a histopathological entity of PTPR that should be recognized and be considered in the differential diagnosis of E955 | VOLUME 60 | NUMBER 5 | MAY 2007 tumors with papillary features that present in the pineal region. The accumulation of further case reports and longer follow-up data is needed to better define this pathological entity regarding its natural course, behavior, treatment options, patterns of recurrence and dissemination, and long-term clinical outcome. REFERENCES 1. Ang LC, Taylor AR, Bergin D, Kaufmann CE: An immunohistochemical study of papillary tumors in the central nervous system. Cancer 65:2712–2719, 1990. 2. Bruce JN, Stein BM: Management of pineal tumors, in Tindall GT, Cooper PR, barrow DL (eds): The Practice of Neurosurgery. Baltimore, Williams and Wilkins, 1996, pp 875–887. 3. Chapman PH, Linggood RM: The management of pineal area tumors: A recent reappraisal. Cancer 46:1253–1257, 1980. 4. Chason JL, Walker FB, Landers JW: Metastatic carcinoma in the central nervous system and dorsal root ganglia. A prospective autopsy study. Cancer 16:781–787, 1963. 5. DeGirolami U, Schmidek H: Clinicopathological study of 53 tumors of the pineal region. J Neurosurg 39:455–462, 1973. 6. France LH: Contribution to the study of 150 cases of cerebral metastasis. II. Neuropathogical study. J Neurosurg Sci 4:189–210, 1975. 7. Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biasette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fevre-Montange M: Papillary tumor of the pineal region. Am J Surg Pathol 27:505–512, 2003. 8. Neuwelt EA: An update on the surgical treatment of malignant pineal region tumors. Clin Neurosurg 32:397–428, 1985. 9. Nguyen LN, Maor MH, Oswald MJ: Brain metastases as the only manifestation of an undetected primary tumor. Cancer 83:2181–2184, 1998. 10. Park SH, Park HR, Chi JG: Papillary ependymoma: Its differential diagnosis from choroid plexus papilloma. J Korean Med Sci 11:415–421, 1996. 11. Regis J, Bouillot P, Rouby-Volot F, Figarella-Branger D, Dufour H, Peragut JC: Pineal region tumors and the role of stereotactic biopsy: Review of the mortality, morbidity, and diagnostic rates in 370 cases. Neurosurgery 39:907–914, 1996. 12. Salvati M, Cervoni L, Raco A: Single brain metastases from unknown primary malignancies in CT-era. J Neurooncol 23:75–80, 1995. 13. Trojanowski JQ, Tascos NA, Rorke LB: Malignant pineocytoma with prominent papillary features. Cancer 50:1789–1793, 1982. 14. Vaquero J, Coca S, Martinez R, Escandon J: Papillary pineocytoma. Case report. J Neurosurg 73:135–137, 1990. Acknowledgment There was no financial support involved during the preparation of this case report. COMMENTS T he authors report three patients who meet the histopathological criteria for the recently described entity, papillary tumors of the pineal region (PTPR). It is a valuable report describing a pathology that needs to be considered in a differential diagnosis of tumors with papillary features that present in the pineal region. The authors note that the cells composing the PTPR are similar to the ependymal cells of the subcommissural organ, which strengthens the hypothesis that this tumor is derived from a specialized ependymocyte associated with the organ. With very limited data, the authors suggest that PTPR do have potential for local recurrence, and they recommend local radiation after resection. This is an excellent, informative report of PTPR that adds significantly to the previous reports. Andrew H. Kaye Melbourne, Australia www.neurosurgery-online.com PAPILLARY PINEAL REGION TUMORS T umors in the pineal region, although rare, are characterized by the wide variety of unusual histological subtypes that can occur in this relatively small area. This article describes three such tumors with histological, immunohistochemical, and ultrastructural features that are similar to a previously described entity called papillary tumor of the pineal region (1). The important part of this report lies in the authors’ approach to work through the differential diagnosis, which included metastatic carcinoma, choroid plexus papilloma/carcinoma, and papillary ependymoma. They provide a clear discussion of how a panel of immunohistochemical stains can be used to differentiate between the different tumors in the differential. Using electron microscopy, they showed the tumor cells had features of secretory cells and ependymal cells. They argue that these features, along with the immunohistochemical profile, suggest that NEUROSURGERY these tumors arise from specialized ependymal cells of the subcommissural organ. This is an interesting speculation that deserves additional consideration. Peter D. Canoll Pathologist Jeffrey N. Bruce New York, New York 1. Jouvet A, Fauchon F, Liberski P, Saint-Pierre G, Didier-Bazes M, Heitzmann A, Delisle MB, Biassette HA, Vincent S, Mikol J, Streichenberger N, Ahboucha S, Brisson C, Belin MF, Fevre-Montange M: Papillary tumor of the pineal region. Am J Surg Pathol 27:505–512, 2003. VOLUME 60 | NUMBER 5 | MAY 2007 | E955